The effects of acute and chronic noise trauma on stimulus-evoked activity across primary auditory cortex layers.

Exposure to intense noise environments is a major cause of sensorineural hearing loss and auditory perception disorders, such as tinnitus and hyperacusis, which may have a central origin. The effects of noise-induced hearing loss on the auditory cortex have been documented in many studies. One limitation of these studies, however, is that the effects of noise trauma have been mostly studied at the granular layer (i.e, the main cortical recipient of thalamic input), while the cortex is a very complex structure, with six different layers each having its own pattern of connectivity and role in sensory processing. The present study aims to investigate the effects of acute and chronic noise trauma on the laminar pattern of stimulus-evoked activity in the primary auditory cortex of the anesthetized guinea pig. We show that acute and chronic noise trauma are both followed by an increase in stimulus-evoked cortical responses, mostly in the granular and supragranular layers. The cortical responses are more monotonic as a function of the intensity level after noise trauma. There was minimal change, if any, in local field potential (LFP) amplitude after acute noise trauma, while LFP amplitude was enhanced after chronic noise trauma. Finally, LFP and the current source density analysis suggest that acute but more specifically chronic noise trauma is associated with the emergence of a new sink in the supragranular layer. This result suggests that supragranular layers become a major input recipient. We discuss the possible mechanisms and functional implications of these changes.NEW & NOTEWORTHY Our study shows that cortical activity is enhanced after trauma and that the sequence of cortical column activation during stimulus-evoked response is altered, i.e. the supragranular layer becomes a major input recipient. We speculate that these large cortical changes may play a key role in the auditory hypersensitivity (hyperacusis) that can be triggered after noise trauma in human subjects.

The Analogy between Tinnitus and Chronic Pain: A Phenomenological Approach.

Tinnitus is an auditory sensation without external acoustic stimulation or significance, which may be lived as an unpleasant experience and impact the subject's quality of life. Tinnitus loudness, which is generally low, bears no relation to distress. Factors other than psychoacoustic (such as psychological factors) are therefore implicated in the way tinnitus is experienced. The aim of this article is to attempt to understand how tinnitus can, like chronic pain, generate a 'crisis' in the process of existence, which may go as far as the collapse of the subject. The main idea put forward in the present article is that tinnitus may be compared to the phenomenon of pain from the point of view of the way it is experienced. Although the analogy between tinnitus and pain has often been made in the literature, it has been limited to a parallel concerning putative physiopathological mechanisms and has never really been explored in depth from the phenomenological point of view. Tinnitus is comparable to pain inasmuch as it is felt, not perceived: it springs up (without intention or exploration), abolishes the distance between the subject and the sensation (there is only a subject and no object), and has nothing to say about the world. Like pain, tinnitus is formless and abnormal and can alter the normal order of the world with maximum intensity. Finally, tinnitus and pain enclose the subject within the limits of the body, which then becomes in excess. Tinnitus may be a source of suffering, which affects not only the body but a person's very existence and, in particular, its deployment in time. Plans are thus abolished, so time is no longer 'secreted', it is enclosed in an eternal present. If the crisis triggered by tinnitus is not resolved, the subject may buckle and collapse (depression) when their resources for resisting are depleted. The path may be long and winding from the moment when tinnitus emerges to when it assaults existence and its eventual integration into a new existential norm where tinnitus is no longer a source of disturbance.

Offset responses in primary auditory cortex are enhanced after notched noise stimulation.

Sensory "aftereffects" are a subgroup of sensory illusions that can be defined as an illusory phenomenon triggered after prolonged exposure to a given sensory inducer. These phenomena are interesting because they can provide insights into the mechanisms of perception. In auditory modality, there is a special interest in the so-called "Zwicker tone" (ZT), an auditory aftereffect triggered after the presentation of a notched noise (NN, broadband noise with a missing frequency band). The ZT has been considered a plausible model of a specific tinnitus subtype since it presents some key characteristics in common with tinnitus. Indeed, both the tinnitus percept and ZT can be triggered by a relative "sensory deprivation," and their pitch corresponds to the frequency region that has been sensory deprived. The effects of a NN presentation on the central auditory system are still barely investigated, and the mechanisms of the ZT are elusive. In this study, we analyzed the laminar structure of the neural activity in the primary cortex of anesthetized and awake guinea pigs during and after white noise (WN) and NN stimulation. We found significantly increased offset responses, in terms of both spiking activity and local field potential amplitude, after NN compared with WN presentation. The offset responses were circumscribed to the granular and upper infragranular layers (input layers) and were maximal when the neuron's best frequency was within or near the missing frequency band. The mechanisms of the offset response and its putative link with the ZT are discussed.NEW & NOTEWORTHY Notched noise (white noise with embedded spectral gap) causes significant excitatory offset responses in the auditory cortex of awake and anesthetized guinea pigs. The largest offset responses were located in the infragranular/granular layers, and current source density analysis revealed that offset responses were associated with an early current sink localized in the upper infragranular layers. We discuss the possibility that the offset responses might be associated with an auditory phantom percept (Zwicker tone).

The Utility of Economic Measures to Quantify the Burden of Tinnitus in Affected Individuals: A Scoping Review.

BACKGROUND AND OBJECTIVES: Tinnitus is a chronic subjective condition that impacts patients' health-related quality of life (HRQoL) and requires multidisciplinary interventions. In health economics, quality-adjusted life years (QALYs) and willingness to pay (WTP) are essential for evaluating treatment effectiveness in cost-effectiveness, cost-utility, or cost-benefit analysis. The extent to which these economic measures have been used in tinnitus research has not been investigated. The objectives of this scoping review were to explore findings and limitations of existing studies and provide an insight into how these economic measures could be used to quantify the burden of tinnitus in affected individuals. METHODS: A scoping review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodological framework. The search strategy involved four electronic databases. Records were included when QALYs or WTP were measured in individuals whose primary or secondary complaint was tinnitus. RESULTS: A total of 15 studies were identified: three WTP assessment studies and 12 QALY assessment studies using direct preference-based measures (PBMs) (n = 4), indirect PBMs (n = 7), and a disease-specific psychometric instrument (n = 1). The limited use to date of PBMs to assess HRQoL in tinnitus patients is an important finding. CONCLUSIONS: Further studies using reliable economic methods and focusing on patients' WTP for treatment or their preference for their current health state are needed. Applying PBMs in tinnitus research is crucial not only for the healthcare decision-making process but also to improve patient-centred care.

The difference in poststimulus suppression between residual inhibition and forward masking.

The phenomenon of tinnitus masking (TM) and residual inhibition (RI) of tinnitus are two ways to investigate how external sounds interact with tinnitus: TM provides insight on the fusion between external sound activity and tinnitus related activity while RI provides insight on how the external sound might suppress the tinnitus related activity for a period of time. Differences in masking level between the tinnitus and an external tone with tinnitus characteristics (frequency, loudness) have previously shown a high level of heterogeneity. The difference in poststimulus suppression between the two, that is, residual inhibition for the former, and forward masking for the latter, has never been explored. This study aims to investigate minimum masking levels (MMLs) and minimum residual inhibition levels (MRILs) of tinnitus and of an external tone mimicking tinnitus while using diotic and dichotic noises. Pulsed narrowband noises (1 octave width and centered at 1kHz, frequency of the hearing loss slope, tinnitus frequency) and white noise were randomly presented to 20 tinnitus participants and 20 controls with an external tone mimicking tinnitus (4kHz, intensity level corresponding to tinnitus loudness). The MML values obtained for the masking of tinnitus and for the mimicking external sounds were very similar. On the other hand, the MRILs were significantly different between the tinnitus and the mimicking external sounds within tinnitus participants. They were also different between the tinnitus participants and the controls. Overall, for both within and between comparisons, the MRIL values were much higher to produce a poststimulus suppression for the mimicking sound than for the tinnitus. The results showed no significant differences between the diotic and dichotic conditions. These results corroborate other findings suggesting that the tinnitus-related neural activity is very different from the stimulus-related neural activity. The consequences of this last finding are discussed.

A contribution to the debate on tinnitus definition.

Tinnitus is generally defined as an auditory perception in the absence of environmental sound stimulation. However, this definition is quite incomplete as it omits an essential aspect, the patient's point of view. This point of view constitutes, first and foremost, a global and unified lived experience, which is not only sensory (localization, loudness, pitch and tone), but also cognitive (thoughts, attentiveness, behaviors) and emotional (discomfort, suffering). This experience can be lived in a very unpleasant way and consequently have a very negative impact on quality of life. This article proposes and justifies a new definition for tinnitus elaborated by a group of French clinicians and researchers, which is more in line with its phenomenology. It also provides a minimum knowledge base, including possibilities for clinical care, hoping to eradicate all misinformation, misconceptions and inappropriate attitudes or practices toward this condition. Here is the short version of our definition: Tinnitus is an auditory sensation without an external sound stimulation or meaning, which can be lived as an unpleasant experience, possibly impacting quality of life.

Modulation of hyperacusis and tinnitus loudness in tinnitus patients with and without hearing loss following 3 weeks of acoustic stimulation: A proof-of-concept study.

Tinnitus and hyperacusis are two debilitating conditions that are highly comorbid. It has been postulated that they may originate from similar pathophysiological mechanisms such as an increase in central gain. Interestingly, sound stimulation has been shown to reduce central gain and is currently used for the treatment of both conditions. This study investigates the effect of sound stimulation on both tinnitus and hyperacusis in the same patients. Two distinct series of tinnitus participants were tested: one with normal or near-normal hearing (n=16) and one with hearing loss (n=14). A broadband noise shaped to cover most of the tinnitus frequency spectrum was delivered through hearing aids using the noise generator feature (no amplification) and verified through real-ear measurements. Participants received sound stimulation for 3 weeks and were tested before (at baseline), then after 1 week and at the end of the 3 weeks of sound stimulation. There was also a 1-month follow-up after the end of the stimulation protocol. The measurements included self-reported measures of tinnitus and hyperacusis (VAS), validated questionnaires (THI, HQ) and psychoacoustic measurements (tinnitus battery and loudness functions). On both self-assessment (VAS of sound tolerance and tinnitus loudness) and psychoacoustic measures (loudness function and tinnitus loudness in dB), about 50% of tinnitus participants had a synchronous (either a decrease or an increase) modulation of hyperacusis and tinnitus loudness after 1 week and 3 weeks of acoustic stimulation and up to about 70% of participants at 1-M follow-up. The decrease of hyperacusis and tinnitus loudness was more prevalent in normal-hearing participants. There was a significant increase in tinnitus loudness during and following the stimulation in the group with hearing loss. Hyperacusis improvement as assessed by loudness function was significantly correlated with the intensity level of the acoustic stimulation (dB level of the noise produced by the noise generator) in tinnitus participants with normal/near-normal hearing thresholds. Our study partly supports the central gain hypothesis by showing synchronous modulation of hyperacusis and tinnitus loudness. It also shows beneficial effects of acoustic stimulation in some tinnitus individuals, in particular those with normal or near-normal hearing, while highlighting the importance of a careful fitting of sound generators to prevent increase. Since the amplification feature was not turned on in our study, future work should determine whether amplification alone, or in addition to acoustic stimulation (sound generators), would benefit to those with hearing loss.

A psychoacoustic test for misophonia assessment.

Misophonia is a condition where a strong arousal response is triggered when hearing specific human generated sounds, like chewing, and/or repetitive tapping noises, like pen clicking. It is diagnosed with clinical interviews and questionnaires since no psychoacoustic tools exist to assess its presence. The present study was aimed at developing and testing a new assessment tool for misophonia. The method was inspired by an approach we have recently developed for hyperacusis. It consisted of presenting subjects (n = 253) with misophonic, pleasant, and unpleasant sounds in an online experiment. The task was to rate them on a pleasant to unpleasant visual analog scale. Subjects were labeled as misophonics (n = 78) or controls (n = 55) by using self-report questions and a misophonia questionnaire, the MisoQuest. There was a significant difference between controls and misophonics in the median global rating of misophonic sounds. On the other hand, median global rating of unpleasant, and pleasant sounds did not differ significantly. We selected a subset of the misophonic sounds to form the core discriminant sounds of misophonia (CDSMiso). A metric: the CDS score, was used to quantitatively measure misophonia, both with a global score and with subscores. The latter could specifically quantify aversion towards different sound sources/events, i.e., mouth, breathing/nose, throat, and repetitive sounds. A receiver operating characteristic analysis showed that the method accurately classified subjects with and without misophonia (accuracy = 91%). The present study suggests that the psychoacoustic test we have developed can be used to assess misophonia reliably and quickly.

A psychoacoustic test for diagnosing hyperacusis based on ratings of natural sounds.

Hyperacusis is defined as an increased sensitivity to sounds, i.e. sounds presented at moderate levels can produce discomfort or even pain. Existing diagnostic methods, like the Hyperacusis Questionnaire (HQ) and Loudness Discomfort Levels (LDLs), have been challenged because of their variability and lack of agreement on appropriate cut-off values. We propose a novel approach by using psychoacoustic ratings of natural sounds as an assessment tool for hyperacusis. Subjects (n = 81) were presented with natural and artificial (tone pips, noises) sounds (n = 69) in a controlled environment at four sound levels (60, 70, 80 and 90 dB SPL). The task was to rate them on a pleasant to unpleasant visual analog scale. The inherent challenge of this study was to create a new diagnostic tool when no gold standard of hyperacusis diagnosis exists. We labeled our subjects as hyperacusic (n = 26) when they were diagnosed as such by at least two of three methods (HQ, LDLs and self-report). There was a significant difference between controls (n = 23) and hyperacusics in the median global rating of pleasant sounds. Median global ratings of unpleasant sounds and artificial sounds did not differ significantly. Then we selected the subset of sounds that could best discriminate the controls from the hyperacusics, the Core Discriminant Sounds (CDS), and we used them to develop a new metric: The CDS score. A normalized global score and a score for each sound level can be computed with respect to a control population without hyperacusis. A receiver operating characteristic analysis showed that the accuracy of our method in distinguishing subjects with and without complaints of hyperacusis (86%, 95% Confidence Interval (CI): 76-93%) is comparable to that of existing methods such as the LDL (77%, CI: 67-86%) and the HQ (80%, CI: 69-88%). We believe that the CDS score is more relevant to subject's complaints than LDLs and that it could be applied in a clinical environment in a fast and effective way, while minimizing discomfort and biases.

Comparing Tinnitus Tuning Curves and Psychoacoustic Tuning Curves.

Tinnitus masking patterns have long been known to differ from those used for masking external sound. In the present study, we compared the shape of tinnitus tuning curves (TTCs) to psychophysical tuning curves (PTCs), the latter using as a target, an external sound that mimics the tinnitus characteristics. A secondary goal was to compare sound levels required to mask tinnitus to those required to mask tinnitus-mimicking sounds. The TTC, PTC, audiometric thresholds, tinnitus pitch, and level matching results of 32 tinnitus patients were analyzed. Narrowband noise maskers were used for both PTC and TTC procedures. Patients were categorized into three groups based on a combination of individual PTC-TTC results. Our findings indicate that in 41% of cases, the PTC was sharp (V shape), but the TTC showed a flat configuration, suggesting that the tinnitus-related activity in that subgroup does not behave as a regular stimulus-induced activity. In 30% of cases, V-shape PTC and TTC were found, indicating that the tinnitus-related activity may share common properties with stimulus-induced activity. For a masker centered at the tinnitus frequency, the tinnitus was more difficult to mask than the mimicking tone in 72% of patients; this was particularly true for the subset with V-shape PTCs and flat TTCs. These results may have implications for subtyping tinnitus and acoustic therapies, in particular those targeting the tinnitus frequency.

An Integrative Model Accounting for the Symptom Cluster Triggered After an Acoustic Shock.

Acoustic shocks and traumas sometimes result in a cluster of debilitating symptoms, including tinnitus, hyperacusis, ear fullness and tension, dizziness, and pain in and outside the ear. The mechanisms underlying this large variety of symptoms remain elusive. In this article, we elaborate on the hypothesis that the tensor tympani muscle (TTM), the trigeminal nerve (TGN), and the trigeminal cervical complex (TCC) play a central role in generating these symptoms. We argue that TTM overuse (due to the acoustic shock), TTM overload (due to muscle tension), and ultimately, TTM injury (due to hypoxia and "energy crisis") lead to inflammation, thereby activating the TGN, TCC, and cortex. The TCC is a crossroad structure integrating sensory inputs coming from the head-neck complex (including the middle ear) and projecting back to it. The multimodal integration of the TCC may then account for referred pain outside the ear when the middle ear is inflamed and activates the TGN. We believe that our model proposes a synthetic and explanatory framework to explain the phenomena occurring postacoustic shock and potentially also after other nonauditory causes. Indeed, due to the bidirectional properties of the TCC, musculoskeletal disorders in the region of the head-neck complex, including neck injury due to whiplash or temporomandibular disorders, may impact the middle ear, thereby leading to otic symptoms. This previously unavailable model type is experimentally testable and must be taken as a starting point for identifying the mechanisms responsible for this particular subtype of tinnitus and its associated symptoms.

A Case of Acoustic Shock with Post-trauma Trigeminal-Autonomic Activation.

This study reports the case of an acoustic shock injury (ASI), which did not result in a significant hearing loss, but was followed by manifold chronic symptoms both within (tinnitus, otalgia, tingling in the ear, tension in the ear, and red tympanum) and outside the ears (blocked nose, pain in the neck/temporal region). We suggest that these symptoms may result from a loop involving injury to middle ear muscles, peripheral inflammatory processes, activation and sensitization of the trigeminal nerve, the autonomic nervous system, and central feedbacks. The pathophysiology of this ASI is reminiscent of that observed in post-traumatic trigeminal-autonomic cephalalgia. This framework opens new and promising perspectives on the understanding and medical management of ASI.

Reactive Neurogenesis and Down-Regulation of the Potassium-Chloride Cotransporter KCC2 in the Cochlear Nuclei after Cochlear Deafferentation.

While many studies have been devoted to investigating the homeostatic plasticity triggered by cochlear hearing loss, the cellular and molecular mechanisms involved in these central changes remain elusive. In the present study, we investigated the possibility of reactive neurogenesis after unilateral cochlear nerve section in the cochlear nucleus (CN) of cats. We found a strong cell proliferation in all the CN sub-divisions ipsilateral to the lesion. Most of the newly generated cells survive up to 1 month after cochlear deafferentation in all cochlear nuclei (except the dorsal CN) and give rise to a variety of cell types, i.e., microglial cells, astrocytes, and neurons. Interestingly, many of the newborn neurons had an inhibitory (GABAergic) phenotype. This result is intriguing since sensory deafferentation is usually accompanied by enhanced excitation, consistent with a reduction in central inhibition. The membrane potential effect of GABA depends, however, on the intra-cellular chloride concentration, which is maintained at low levels in adults by the potassium chloride co-transporter KCC2. The KCC2 density on the plasma membrane of neurons was then assessed after cochlear deafferentation in the cochlear nuclei ipsilateral and contralateral to the lesion. Cochlear deafferentation is accompanied by a strong down-regulation of KCC2 ipsilateral to the lesion at 3 and 30 days post-lesion. This study suggests that reactive neurogenesis and down-regulation of KCC2 is part of the vast repertoire involved in homeostatic plasticity triggered by hearing loss. These central changes may also play a role in the generation of tinnitus and hyperacusis.

Membrane potential dynamics of populations of cortical neurons during auditory streaming.

How a mixture of acoustic sources is perceptually organized into discrete auditory objects remains unclear. One current hypothesis postulates that perceptual segregation of different sources is related to the spatiotemporal separation of cortical responses induced by each acoustic source or stream. In the present study, the dynamics of subthreshold membrane potential activity were measured across the entire tonotopic axis of the rodent primary auditory cortex during the auditory streaming paradigm using voltage-sensitive dye imaging. Consistent with the proposed hypothesis, we observed enhanced spatiotemporal segregation of cortical responses to alternating tone sequences as their frequency separation or presentation rate was increased, both manipulations known to promote stream segregation. However, across most streaming paradigm conditions tested, a substantial cortical region maintaining a response to both tones coexisted with more peripheral cortical regions responding more selectively to one of them. We propose that these coexisting subthreshold representation types could provide neural substrates to support the flexible switching between the integrated and segregated streaming percepts.

Revisiting the cochlear and central mechanisms of tinnitus and therapeutic approaches.

This short review aims at revisiting some of the putative mechanisms of tinnitus. Cochlear-type tinnitus is suggested to result from aberrant activity generated before or at the cochlear nerve level. It is proposed that outer hair cells, through their role in regulating the endocochlear potential, can contribute to the enhancement of cochlear spontaneous activity. This hypothesis is attractive as it provides a possible explanation for cochlear tinnitus of different aetiologies, such as tinnitus produced by acute noise trauma, intense low-frequency sounds, middle-ear dysfunction or temporomandibular joint disorders. Other mechanisms, namely an excitatory drift in the operating point of the inner hair cells and activation of NMDA receptors, are also briefly reported. Central-type tinnitus is supposed to result from aberrant activity generated in auditory centres, i.e. in these patients, the tinnitus-related activity does not pre-exist in the cochlear nerve. A reduction in cochlear activity due to hearing loss is suggested to produce tinnitus-related plastic changes, namely cortical reorganisation, thalamic neuron hyperpolarisation, facilitation of non-auditory inputs and/or increase in central gain. These central changes can be associated with abnormal patterns of spontaneous activity in the auditory pathway, i.e. hyperactivity, hypersynchrony and/or oscillating activity. Therapeutic approaches aimed at reducing cochlear activity and/or tinnitus-related central changes are discussed.

Dynamic representation of spectral edges in guinea pig primary auditory cortex.

The central representation of a given acoustic motif is thought to be strongly context dependent, i.e., to rely on the spectrotemporal past and present of the acoustic mixture in which it is embedded. The present study investigated the cortical representation of spectral edges (i.e., where stimulus energy changes abruptly over frequency) and its dependence on stimulus duration and depth of the spectral contrast in guinea pig. We devised a stimulus ensemble composed of random tone pips with or without an attenuated frequency band (AFB) of variable depth. Additionally, the multitone ensemble with AFB was interleaved with periods of silence or with multitone ensembles without AFB. We have shown that the representation of the frequencies near but outside the AFB is greatly enhanced, whereas the representation of frequencies near and inside the AFB is strongly suppressed. These cortical changes depend on the depth of the AFB: although they are maximal for the largest depth of the AFB, they are also statistically significant for depths as small as 10 dB. Finally, the cortical changes are quick, occurring within a few seconds of stimulus ensemble presentation with AFB, and are very labile, disappearing within a few seconds after the presentation without AFB. Overall, this study demonstrates that the representation of spectral edges is dynamically enhanced in the auditory centers. These central changes may have important functional implications, particularly in noisy environments where they could contribute to preserving the central representation of spectral edges.

Enhanced representation of spectral contrasts in the primary auditory cortex.

The role of early auditory processing may be to extract some elementary features from an acoustic mixture in order to organize the auditory scene. To accomplish this task, the central auditory system may rely on the fact that sensory objects are often composed of spectral edges, i.e., regions where the stimulus energy changes abruptly over frequency. The processing of acoustic stimuli may benefit from a mechanism enhancing the internal representation of spectral edges. While the visual system is thought to rely heavily on this mechanism (enhancing spatial edges), it is still unclear whether a related process plays a significant role in audition. We investigated the cortical representation of spectral edges, using acoustic stimuli composed of multi-tone pips whose time-averaged spectral envelope contained suppressed or enhanced regions. Importantly, the stimuli were designed such that neural responses properties could be assessed as a function of stimulus frequency during stimulus presentation. Our results suggest that the representation of acoustic spectral edges is enhanced in the auditory cortex, and that this enhancement is sensitive to the characteristics of the spectral contrast profile, such as depth, sharpness and width. Spectral edges are maximally enhanced for sharp contrast and large depth. Cortical activity was also suppressed at frequencies within the suppressed region. To note, the suppression of firing was larger at frequencies nearby the lower edge of the suppressed region than at the upper edge. Overall, the present study gives critical insights into the processing of spectral contrasts in the auditory system.

Spatiotemporal coordination of slow-wave ongoing activity across auditory cortical areas.

Natural acoustic stimuli contain slow temporal fluctuations, and the modulation of ongoing slow-wave activity by bottom-up and top-down factors plays essential roles in auditory cortical processing. However, the spatiotemporal pattern of intrinsic slow-wave activity across the auditory cortical modality is unknown. Using in vivo voltage-sensitive dye imaging in anesthetized guinea pigs, we measured spectral tuning to acoustic stimuli across several core and belt auditory cortical areas, and then recorded spontaneous activity across this defined network. We found that phase coherence in spontaneous slow-wave (delta-theta band) activity was highest between regions of core and belt areas that had similar frequency tuning, even if they were distant. Further, core and belt regions with high phase coherence were phase shifted. Interestingly, phase shifts observed during spontaneous activity paralleled latency differences for evoked activity. Our findings suggest that the circuits underlying this intrinsic source of slow-wave activity support coordinated changes in excitability between functionally matched but distributed regions of the auditory cortical network.

Tinnitus-related neural activity: theories of generation, propagation, and centralization.

The neuroscience of tinnitus represents an ideal model to explore central issues in brain functioning such as the formation of auditory percepts, in addition to opening up new treatment avenues for the condition in the long-term. The present review discusses the origin and nature of tinnitus-related neural activity. First, we review evidence for the hypothesis that tinnitus is caused by the central nervous system changes induced by sensory deprivation, even when hearing loss is not visible in the audiogram. Second, we suggest that changes in neural activity in individual central structures may not be sufficient to underlie the tinnitus percept. Instead, we propose that tinnitus may arise from functional alterations at multiple levels which promote abnormal propagation of neural activity throughout the network involved in auditory perception. In this context, functional coupling within and between central auditory structures may be especially important to consider. Investigating how sensory deprivation affects functional coupling between areas, which might be reflected in changes in temporal coherence of intrinsic ongoing activity patterns, may give critical insights into the mechanisms of tinnitus.

Increasing spectrotemporal sound density reveals an octave-based organization in cat primary auditory cortex.

Auditory neurons are likely adapted to process complex stimuli, such as vocalizations, which contain spectrotemporal modulations. However, basic properties of auditory neurons are often derived from tone pips presented in isolation, which lack spectrotemporal modulations. In this context, it is unclear how to deduce the functional role of auditory neurons from their tone pip-derived tuning properties. In this study, spectrotemporal receptive fields (STRFs) were obtained from responses to multi-tone stimulus ensembles differing in their average spectrotemporal density (i.e., number of tone pips per second). STRFs for different stimulus densities were derived from multiple single-unit activity (MUA) and local field potentials (LFPs), simultaneously recorded in primary auditory cortex of cats. Consistent with earlier studies, we found that the spectral bandwidth was narrower for MUA compared with LFPs. Both neural firing rate and LFP amplitude were reduced when the density of the stimulus ensemble increased. Surprisingly, we found that increasing the spectrotemporal sound density revealed with increasing clarity an over-representation of response peaks at frequencies of approximately 3, 5, 10, and 20 kHz, in both MUA- and LFP-derived STRFs. Although the decrease in spectral bandwidth and neural activity with increasing stimulus density can likely be accounted for by forward suppression, the mechanisms underlying the over-representation of the octave-spaced response peaks are unclear. Plausibly, the over-representation may be a functional correlate of the periodic pattern of corticocortical connections observed along the tonotopic axis of cat auditory cortex.